p(HGNC:IL1B)
The plaque-associated microglia secrete a variety of cytotoxic species including the inflammatory cytokines, INF-g, TNF-a, IL-1b and IL-6 and chemokines, most prominently CCL2 [10-12]. PubMed:21718217
Anatabine at 200 mg/ ml significantly lowered LPS induced IL-1b levels in whole blood (Mann–Whitney U=0.0, Z=-2.3, P=0.02) PubMed:23178521
Higher doses of anatabine resulted in a complete suppression of IL-1b levels in LPS challenged human blood (Mann–Whitney U=0.0, Z=-2.5, P=0.01) PubMed:23178521
Anatabine at 200 mg/ ml significantly lowered LPS induced IL-1b levels in whole blood (Mann–Whitney U=0.0, Z=-2.3, P=0.02) PubMed:23178521
NFT containing neurons upregulated genes involved in cell survival and viability, inflammation, cell cycle progression and molecular transport and downregulated apoptosis, necrosis and cell death pathways (Figure 1a). NFkB, a pro-survival master transcriptional regulator of inflammation, was the highest predicted upstream regulator of the NFT-gene expression profile. In agreement with inflammatory activation, other predicted upstream regulators included IFNG, TNF, TLR4, IL1B and CXCL1 (Figure 1b) PubMed:30126037
Activation of NLRP3 leads to the generation of interleukin-1b (IL-1b) and interleukin 18 (IL-18), which are being cleaved by caspase-1 from their inactive precursors and subsequently PubMed:28019679
Using the herbizide, N,N0-dimethyl-4,40-bipyridinium dichloride (paraquat) as a mitochondrial toxin, which is known to induce oxidative stress, Chen et al. found increased levels of caspase-1 and IL-1b in brain of wild type and APP/PS1 transgenic mice (2), suggesting that those were due to NLRP3 inflammasome activation PubMed:28019679
Using the herbizide, N,N0-dimethyl-4,40-bipyridinium dichloride (paraquat) as a mitochondrial toxin, which is known to induce oxidative stress, Chen et al. found increased levels of caspase-1 and IL-1b in brain of wild type and APP/PS1 transgenic mice (2), suggesting that those were due to NLRP3 inflammasome activation PubMed:28019679
Activation of NLRP3 leads to the generation of interleukin-1b (IL-1b) and interleukin 18 (IL-18), which are being cleaved by caspase-1 from their inactive precursors and subsequently PubMed:28019679
In addition, high extracellular levels of K+ can block IL-1β release after NLRC4 and AIM2 inflammasome formation80,81, which indicates that low intracellular K+ levels might also be required for the activation of these inflammasomes. PubMed:23702978
In addition, type I IFNs can reduce IL-1β and IL-18 release by functioning at two levels. PubMed:23702978
IFNs upregulate AIM2 expression but they downregulate IL-1β expression and inhibit the NLRP3 inflammasome. PubMed:23702978
For inflammasome activation and IL-1β release, autophagy is a negative regulator: PubMed:23702978
Inflammasomes are key signalling platforms that detect pathogenic microorganisms and sterile stressors, and that activate the highly pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18. PubMed:23702978
Once the protein complexes have formed, the inflammasomes activate caspase 1, which proteolytically activates the pro-inflammatory cytokines interleukin-1β (IL-1β)3 and IL-18. PubMed:23702978
Active caspase 1 proteolytically activates a number of proteins8, including pro-IL-1β and pro-IL-18 (REFS 9,10), and induces their release via a non-classical secretion pathway11. PubMed:23702978
Active caspase 1 proteolytically activates a number of proteins8, including pro-IL-1β and pro-IL-18 (REFS 9,10), and induces their release via a non-classical secretion pathway11. PubMed:23702978
Caspase 1mediated activation of members of the IL-1β cytokine family leads to the recruitment and the activation of other immune cells, such as neutrophils, at the site of infection and/or tissue damage. PubMed:23702978
One additional factor that can mediate IL-1β processing and activation is caspase 8 (FIG. 1) PubMed:23702978
In the presence of the translation inhibitor cycloheximide, TRIF signalling that is downstream of TLR3 or TLR4 leads to pro-IL-1β processing by caspase 8 (REF. 55). PubMed:23702978
In addition, it was recently shown that CD95 signalling mediates IL-1β and IL-18 processing through the activation of caspase 8 (REF. 60) (FIG. 1). PubMed:23702978
For example, following sensing of fungal components by the PRR dectin 1 that is expressed on human dendritic cells, signalling via the kinase SYK leads to the formation of a complex that is composed of caspase 8 and mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1); this complex binds to ASC, which possibly recruits cleavage substrates53. The MALT1-ASC-caspase 8 complex directly mediates IL-1β maturation53. PubMed:23702978
First, a bacterial Toll-like receptor (TLR) activator leads to cellular priming and upregulation of NLRP3 and pro-IL-1β expression (the priming checkpoint in the standard model)37,38. PubMed:23702978
CARD17 (also known as INCA), which is another decoy protein, is upregulated by IFNγ to suppress IL-1β generation114. PubMed:23702978
Indeed, activation of the TNFR family member CD95 (also known as FAS) can induce IL-1β processing that is independent of inflammasomes and of caspase 1 (REF. 59). PubMed:23702978
The transcription of pro-IL-1β is induced by the activation of the transcription factor nuclear factor-κB (NF-κB), whereas pro-IL-18 is constitutively expressed and its expression is increased after cellular activation. PubMed:23702978
Indeed, a number of non-caspase proteases such as proteinase 3 have the ability to activate IL-1β in an inflammasome-independent manner11. PubMed:23702978
The formation of this complex activates RIP3, which is necessary for the cleavage of pro-IL-1β by both the NLRP3-caspase 1 and the caspase 8 pathways56 (FIG. 1). PubMed:23702978
These studies highlighted the role of saturated fatty acids in the production of IL-1β by inflammasomes, i.e. NLRC4 PubMed:24561250
Probenecid, an inhibitor of pannexin 1, has been shown to significantly inhibit the expression and activation of the NLRP2 inflammasome, and the maturation of bothIL-1β and IL-18 in human astrocytes induced by ATP (Minkiewicz et al., 2013) PubMed:24561250
Aging, another risk factor of AD, has been found to activate the NLRP1 inflammasome and upregulate IL-18 and IL-1β levels in the hippocampus of aged mice (Mawhinney et al., 2011) PubMed:24561250
In the CNS, the production of IL-1β by inflammasomes, specifically NLRP1, NLRP2, NLRP3 and NLRC4, is well-characterized as compared to other interleukins (Minkiewicz et al., 2013; Trendelenburg, 2008) PubMed:24561250
Palmitate, a fatty acid, activates the NLRC4 inflammasome in primary astrocytes leading to the release of IL-1β (Liu and Chan, 2014) PubMed:24561250
Recently we identify that palmitate activates the NLRC4 inflammasome in primary astrocytes to release IL-1β, and ASC participates in the activation of the NLRC4 inflammasome (Liu and Chan, 2014) PubMed:24561250
These studies highlighted the role of saturated fatty acids in the production of IL-1β by inflammasomes, i.e. NLRC4 PubMed:24561250
In the CNS, the production of IL-1β by inflammasomes, specifically NLRP1, NLRP2, NLRP3 and NLRC4, is well-characterized as compared to other interleukins (Minkiewicz et al., 2013; Trendelenburg, 2008) PubMed:24561250
Spinal cord injury can activate the NLRP1 inflammasome to produce IL-1β in rat spinal cord neurons (de Rivero Vaccari et al., 2008) PubMed:24561250
Spinal cord injury causes IL-18 and IL-1β release from neuronal cells through the activation of the NLRP1 inflammasome, composed of receptor NLRP1, adaptor protein ASC, caspase-1, caspase-11 and X-linked inhibitor of apoptosis protein (de Rivero Vaccari et al., 2008) PubMed:24561250
In the CNS, the production of IL-1β by inflammasomes, specifically NLRP1, NLRP2, NLRP3 and NLRC4, is well-characterized as compared to other interleukins (Minkiewicz et al., 2013; Trendelenburg, 2008) PubMed:24561250
In vivo and cell studies demonstrate that fibrillar Aβ activates the NLRP3 inflammasome which is composed of the NLRP3 receptor, ASC and caspase-1, to produce IL-1β in microglia (Halle et al., 2008) PubMed:24561250
Inflammasomes involve in the maturation of IL-1β and IL-18 are expressed in neurons (de Rivero Vaccari et al., 2008; Yang-Wei Fann et al., 2013; Zou and Crews, 2012) PubMed:24561250
IL-1β and IL-18 are synthesized as inactive precursors, proIL-1β and proIL-18, respectively, and require inflammasomes for their maturation PubMed:24561250
However the maturation of IL-18 and IL-1β could be regulated by the same type of inflammasome PubMed:24561250
Caspase-1 is the protease that cleaves the precursor of the proinflammatory molecules to form their mature form, such as IL-1β and IL-18 (Schroder and Tschopp, 2010) PubMed:24561250
For example, down-regulation of NLRP1 in macrophages trigger by Cordyceps sinensis mycelium reduces both IL-18 and IL-1β levels (Huang et al., 2013) PubMed:24561250
ASC neutralization reduces the upregulation in IL-18 and IL-1β levels (de Rivero Vaccari et al., 2008) PubMed:24561250
Reducing NLRC4 or ASC levels in the palmitate (PA)-treated astrocytes significantly reduces IL-1β production (Liu and Chan, 2014) PubMed:24561250
Reducing NLRC4 or ASC levels in the palmitate (PA)-treated astrocytes significantly reduces IL-1β production (Liu and Chan, 2014) PubMed:24561250
In the CNS, the production of IL-1β by inflammasomes, specifically NLRP1, NLRP2, NLRP3 and NLRC4, is well-characterized as compared to other interleukins (Minkiewicz et al., 2013; Trendelenburg, 2008) PubMed:24561250
In human astrocytes, ATP released from damaged or dying cells after traumatic brain injury activates the NLRP2 inflammasome, leading to the maturation of both IL-1β and IL-18 (Minkiewicz et al., 2013) PubMed:24561250
The ATP-induced activation of the NLRP2 inflammasome interacts with the ATP-release pannexin 1 channel and ATP-gated P2X7 receptor leading to the maturation of IL-1β (Minkiewicz et al., 2013) PubMed:24561250
Probenecid, an inhibitor of pannexin 1, has been shown to significantly inhibit the expression and activation of the NLRP2 inflammasome, and the maturation of bothIL-1β and IL-18 in human astrocytes induced by ATP (Minkiewicz et al., 2013) PubMed:24561250
However, upon further study of purinergic receptor P2X4 knockout mice with spinal cord injury, the production of IL-1β but not of IL-18 reduces in the neurons as compared with wild-type mice (de Rivero Vaccari et al., 2012) PubMed:24561250
P2X4 knock-out mice has been shown to decrease the level of IL-1β and to have impair inflammasome signaling (de Rivero Vaccari et al., 2012) PubMed:24561250
Interleukins, in particular IL-1β and IL-18, are upregulated in AD brain, and the overexpression of IL-1β or IL-18 is critical for the onset of the inflammatory process (Rubio-Perez and Morillas-Ruiz, 2012), and both mediate the expression of a vast array of inflammatory genes (Weber et al., 2010) PubMed:24561250
Spinal cord injury causes IL-18 and IL-1β release from neuronal cells through the activation of the NLRP1 inflammasome, composed of receptor NLRP1, adaptor protein ASC, caspase-1, caspase-11 and X-linked inhibitor of apoptosis protein (de Rivero Vaccari et al., 2008) PubMed:24561250
NO can also bring about apoptosis of hippocampal neurons via caspase- 3 activity [50] whereas astrocyte-secreted IL-1 beta can increase the production of APP and A beta from neu- rons [51–53] (Fig. 1). PubMed:27314526
It is noteworthy that IL-1 beta and IL-18 can activate various cell types, par- ticularly astrocytes and microglia to induce additional cytokine release involving IL-1 beta , IL-6, and IL-18, and also nitric oxide (NO) synthase that can stimulate production of free radical NO, leading to the forma- tion of peroxynitrite that denatures DNA and impairs cellular energy pathways [48, 49]. PubMed:27314526
It is noteworthy that IL-1 beta and IL-18 can activate various cell types, par- ticularly astrocytes and microglia to induce additional cytokine release involving IL-1 beta , IL-6, and IL-18, and also nitric oxide (NO) synthase that can stimulate production of free radical NO, leading to the forma- tion of peroxynitrite that denatures DNA and impairs cellular energy pathways [48, 49]. PubMed:27314526
Inflammasomes are responsible for the maturation of pro-inflammatory cytokines such as interleukin (IL)-1beta, IL-18, and IL-33 and activation of inflammatory cell death, pyroptosis. PubMed:27314526
Post activation of the inflammasome, caspase 1 enzyme initiates the maturation of pro-inflammatory cytokines particularly interleukin (IL)-1beta, IL-18, and IL-33 [4] (Fig. 1),and inflammation mediated cell death occurs via the nucleotide-binding domain and leucine-rich repeat(NLR) family of proteins [5]. PubMed:27314526
In AD, microglial cells and astrocytes express NLRP3, which in turn can detect A beta plaques and act by secreting caspase-1 to activate IL-1 beta and IL- 18 [23–25]. PubMed:27314526
Both IL-1 beta and IL-18 are generated in their mature secreted form by caspase-1 through activa- tion of the inflammasome. PubMed:27314526
Once activated, caspase-1 promotes the maturation of the proin- flammatory cytokines IL-1 beta , IL-18, and IL-33. PubMed:27314526
Increased levels of IL-1 beta and IL-18 have been detected in serum, cerebrospinal fluid, and brains of patients with AD and in other forms of dementia [42–46]. PubMed:27314526
Increased levels of IL-1 beta and IL-18 have been detected in serum, cerebrospinal fluid, and brains of patients with AD and in other forms of dementia [42–46]. PubMed:27314526
Furthermore, it disrupted the activity of NF-B, and thus, caused the suppression of NO synthase and inflammatory regulators such as IL-6 and IL-1, and the reduction of microglial activation [37] PubMed:29179999
Amyloid-β also induces microglial activation that results in NF-κB – induced expression of pro-inflammatory cytokines such as TNFα, IL1β, IL6, and IL8 from the microglia resulting in neuronal death PubMed:28745240
It is well established that NF-κB is one of the most prominent transcription factors that regulates IL1β production PubMed:28745240
Amyloid-β also induces microglial activation that results in NF-κB – induced expression of pro-inflammatory cytokines such as TNFα, IL1β, IL6, and IL8 from the microglia resulting in neuronal death PubMed:28745240
The expression of pro-inflammatory cytokines such as TNF-, IL-1 and IL-6 were significantly reduced by treatment of 1,8-cineole in A 25-35-induced cells [250]. PubMed:29179999
Glial activation, pro-inflammatory gene expression and elevated secretion of IL-1, IL-6 and TNF- are consequences of high A levels [30,31]. PubMed:29179999
Geniposide considerably suppressed RAGE-related signaling such as ERK and IB/NF-B, the expression of TNF-, IL-1 and cerebral A accumulation in vivo[245] PubMed:29179999
Xanthoceraside decreased the expression of A 25-35/IFN--stimulated NO, IL-1,and TNF- in microglia, which implicated the down-regulation of the activities of MAPK and NF-B pathways [248] PubMed:29179999
It attenuated the development of AD by inhibiting glycogen synthase kinase 3 (GSK-3) and NF-B activation, and sup-pressing the NLRP3 inflammasome and cytokines such as TNF-and IL-1 [1]. PubMed:29179999
It ameliorated spatial learning and memory disorder, which was caused by A 1-42 and was associated with the inter-ference of NF-B activity and the inhibition of IL-1 and TNF-expression [183]. PubMed:29179999
LPS treatment induced the nuclear translocation of NF-κB and increased the expression and secretion of TNF-α and IL-1β [63]. PubMed:27288790
LPS treatment induced the nuclear translocation of NF-κB and increased the expression and secretion of TNF-α and IL-1β [63]. PubMed:27288790
Then the stimulation of RAGE is able to activate the mitogen-activated protein kinase signaling cascades which converge in IκB kinase complex to phosphorylate IκB, thereby release and activate NF-κB, thus trigger NF-κB dependent gene transcription including IL-1β and TNF-α, which in turn induce the translocation of NF-κB to the nucleus [50]. PubMed:27288790
TNF-α [27], IL-1β [28], IL-18 [29], CXCL10 [30] and TGF-β1 [31] are known to be elevated in the AD brain. PubMed:27288790
Increased presence of NF-κB mediated IL-1β, IL-6, and TNF-α cytokines have been reported in the affected tissues, serum and CSF of AD patients PubMed:25652642
Increased presence of NF-κB mediated IL-1β, IL-6, and TNF-α cytokines have been reported in the affected tissues, serum and CSF of AD patients PubMed:25652642
. Heme activates macrophages inducing the production of TNF, KC (Figueiredo et al., 2007), IL-1β (unpublished), and LTB4 (Monteiro et al., 2011). PubMed:24904418
Likewise, heme and FeNTA treatment causes the induction of the M1 markers MHCII, CD86, CD14, TNFα, IL-6, and IL1β and a decrease in the M2 markers CD206, IL-10, and Arginase-1 (the last with FeNTA only) in M0 BMDMs (Figure 3A; supplemental Figures 5, 6A, and 7). PubMed:26675351
For example, monocytes from SCD patients show an enhanced state of activation, with increased expression of interleukin (IL)-15 and production of TNFα and IL-1β. PubMed:26675351
IL-1b participates in a robust inflammatory response. PubMed:24464629
Cotreatment of M0 BMDMs with heme and TAK-242 attenuated the increase of the M1 markers MHCII, CD14, TNFα, IL-6, IL-1β, and CD86 and the decrease of the M2 marker CD206, IL-10, and Ym1 in comparison with heme treatment alone ( Figure 4A; supplemental Figures 5 and 12). PubMed:26675351
Moreover, IL-1β and TNF modifies the hypothalamus threshold of the body temperature causing fever. PubMed:24904418
Caspase 1mediated activation of members of the IL-1β cytokine family leads to the recruitment and the activation of other immune cells, such as neutrophils, at the site of infection and/or tissue damage. PubMed:23702978
Inflammasomes involve in the maturation of IL-1β and IL-18 are expressed in neurons (de Rivero Vaccari et al., 2008; Yang-Wei Fann et al., 2013; Zou and Crews, 2012) PubMed:24561250
Interleukins, in particular IL-1β and IL-18, are upregulated in AD brain, and the overexpression of IL-1β or IL-18 is critical for the onset of the inflammatory process (Rubio-Perez and Morillas-Ruiz, 2012), and both mediate the expression of a vast array of inflammatory genes (Weber et al., 2010) PubMed:24561250
Interleukins, in particular IL-1β and IL-18, are upregulated in AD brain, and the overexpression of IL-1β or IL-18 is critical for the onset of the inflammatory process (Rubio-Perez and Morillas-Ruiz, 2012), and both mediate the expression of a vast array of inflammatory genes (Weber et al., 2010) PubMed:24561250
Increased levels of IL-1 beta and IL-18 have been detected in serum, cerebrospinal fluid, and brains of patients with AD and in other forms of dementia [42–46]. PubMed:27314526
Increased levels of IL-1 beta and IL-18 have been detected in serum, cerebrospinal fluid, and brains of patients with AD and in other forms of dementia [42–46]. PubMed:27314526
It is noteworthy that IL-1 beta and IL-18 can activate various cell types, par- ticularly astrocytes and microglia to induce additional cytokine release involving IL-1 beta , IL-6, and IL-18, and also nitric oxide (NO) synthase that can stimulate production of free radical NO, leading to the forma- tion of peroxynitrite that denatures DNA and impairs cellular energy pathways [48, 49]. PubMed:27314526
It is noteworthy that IL-1 beta and IL-18 can activate various cell types, par- ticularly astrocytes and microglia to induce additional cytokine release involving IL-1 beta , IL-6, and IL-18, and also nitric oxide (NO) synthase that can stimulate production of free radical NO, leading to the forma- tion of peroxynitrite that denatures DNA and impairs cellular energy pathways [48, 49]. PubMed:27314526
NO can also bring about apoptosis of hippocampal neurons via caspase- 3 activity [50] whereas astrocyte-secreted IL-1 beta can increase the production of APP and A beta from neu- rons [51–53] (Fig. 1). PubMed:27314526
NO can also bring about apoptosis of hippocampal neurons via caspase- 3 activity [50] whereas astrocyte-secreted IL-1 beta can increase the production of APP and A beta from neu- rons [51–53] (Fig. 1). PubMed:27314526
Amyloid-β also induces microglial activation that results in NF-κB – induced expression of pro-inflammatory cytokines such as TNFα, IL1β, IL6, and IL8 from the microglia resulting in neuronal death PubMed:28745240
TNF-α [27], IL-1β [28], IL-18 [29], CXCL10 [30] and TGF-β1 [31] are known to be elevated in the AD brain. PubMed:27288790
Nuclear local- ization of NF-κB in differentiated neuron progenitor cells (NPCs) is in- creasing following exposure to IL-1β and TNF-α, strong inducers of the NF-κB pathway with increase in the phosphorylation of IKK and p65 while decrease in the level of IκB [32]. PubMed:27288790
Then the stimulation of RAGE is able to activate the mitogen-activated protein kinase signaling cascades which converge in IκB kinase complex to phosphorylate IκB, thereby release and activate NF-κB, thus trigger NF-κB dependent gene transcription including IL-1β and TNF-α, which in turn induce the translocation of NF-κB to the nucleus [50]. PubMed:27288790
Nuclear local- ization of NF-κB in differentiated neuron progenitor cells (NPCs) is in- creasing following exposure to IL-1β and TNF-α, strong inducers of the NF-κB pathway with increase in the phosphorylation of IKK and p65 while decrease in the level of IκB [32]. PubMed:27288790
Nuclear local- ization of NF-κB in differentiated neuron progenitor cells (NPCs) is in- creasing following exposure to IL-1β and TNF-α, strong inducers of the NF-κB pathway with increase in the phosphorylation of IKK and p65 while decrease in the level of IκB [32]. PubMed:27288790
Nuclear local- ization of NF-κB in differentiated neuron progenitor cells (NPCs) is in- creasing following exposure to IL-1β and TNF-α, strong inducers of the NF-κB pathway with increase in the phosphorylation of IKK and p65 while decrease in the level of IκB [32]. PubMed:27288790
Inhibition of NF-κB leads to decreased induction of cytokines and chemokines by IL-1β and TNF-α. PubMed:27288790
Inhibition of NF-κB leads to decreased induction of cytokines and chemokines by IL-1β and TNF-α. PubMed:27288790
Increased presence of NF-κB mediated IL-1β, IL-6, and TNF-α cytokines have been reported in the affected tissues, serum and CSF of AD patients PubMed:25652642
IL-1b participates in a robust inflammatory response. PubMed:24464629
Moreover, IL-1β and TNF modifies the hypothalamus threshold of the body temperature causing fever. PubMed:24904418
Although KC and IL-1β functions were not investigated during heme-induced inflammatory effects, TNF and LTB4 were described as essential inflammatory mediators during inflammatory events induced by heme. PubMed:24904418
Pro-inflammatory cytokines and chemokines [e.g., inter leukin 1B (IL1B), CXCL8 (also termed IL8), TNF and chemokine (C-C motif) ligand 2 (CCL2, also termed MCP1)], are upregulated in haemolytic disorders such as SCD (Qari et al, 2012). This pro-inflammatory cytokine milieu is crucial in mediating the pro-coagulant effects of vascular endothelial cells and promotes localized inflammation and thrombosis (Qari et al, 2012). PubMed:25307023
Pro-inflammatory cytokines and chemokines [e.g., inter leukin 1B (IL1B), CXCL8 (also termed IL8), TNF and chemokine (C-C motif) ligand 2 (CCL2, also termed MCP1)], are upregulated in haemolytic disorders such as SCD (Qari et al, 2012). This pro-inflammatory cytokine milieu is crucial in mediating the pro-coagulant effects of vascular endothelial cells and promotes localized inflammation and thrombosis (Qari et al, 2012). PubMed:25307023
For example, monocytes from SCD patients show an enhanced state of activation, with increased expression of interleukin (IL)-15 and production of TNFα and IL-1β. PubMed:26675351
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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.